Viruses possess specific conserved regions known as RNA recognition motifs, which are shared within taxonomic groups. Applying these to the Baltimore virus classification system, there are genes/proteins that serve as...
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Single-cell multi-omics is a transformative technology that measures both gene expression and chromatin accessibility in individual cells. However, most studies concentrate on a single tissue and are unable to determi...
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New in silico tools that make use of genome-scale metabolic flux modeling are improving the design of metabolic engineering strategies. This review highlights the latest developments in this area, explains the interfa...
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New in silico tools that make use of genome-scale metabolic flux modeling are improving the design of metabolic engineering strategies. This review highlights the latest developments in this area, explains the interface between these in silico tools and the experimental implementation tools of metabolic engineers, and provides a way forward so that in silico predictions can better mimic reality and more experimental methods can be considered in simulation studies. The several methodologies for solving genome-scale models (eg, flux balance analysis [FBA], parsimonious FBA, flux variability analysis, and minimization of metabolic adjustment) all have unique advantages and applications. There are two basic approaches to designing metabolic engineering strategies in silico, and both have demonstrated success in the literature. The first involves: 1) making a genetic manipulation in a model; 2) testing for improved performance through simulation; and 3) iterating the process. The second approach has been used in more recently designed in silico tools and involves: 1) comparing metabolic flux profiles of a wild-type and ideally engineered state and 2) designing engineering strategies based on the differences in these flux profiles. Improvements in genome-scale modeling are anticipated in areas such as the inclusion of all relevant cellular machinery, the ability to understand and anticipate the results of combinatorial enrichment experiments, and constructing dynamic and flexible biomass equations that can respond to environmental and genetic manipulations.
Background. The processes involved in the somatic assembly of antigen receptor genes are unique to the immune system and are driven largely by random events. Subtle biases, however, may exist and provide clues to the ...
Background. The processes involved in the somatic assembly of antigen receptor genes are unique to the immune system and are driven largely by random events. Subtle biases, however, may exist and provide clues to the molecular mechanisms involved in their assembly and selection. Large-scale efforts to provide baseline data about the genetic characteristics of immunoglobulin (Ig) genes and the mechanisms involved in their assembly have recently become possible due to the rapid growth of genetic databases. Results. We gathered and analyzed nearly 6,500 productive human Ig heavy chain genes and compared them with 325 non-productive Ig genes that were originally rearranged out of frame and therefore incapable of being biased by selection. We found evidence for differences in n-nucleotide tract length distributions which have interesting interpretations for the mechanisms involved in n-nucleotide polymerization. Additionally, we found striking statistical evidence for pairing preferences among D and J segments. We present a statistical model to support our hypothesis that these pairing biases are due to multiple sequential D-to-J rearrangements. Conclusion. We present here the most precise estimates of gene segment usage frequencies currently available along with analyses regarding n-nucleotide distributions and D-J segment pair preferences. Additionally, we provide the first statistical evidence that sequential D-J recombinations occur at the human heavy chain locus during B-cell ontogeny with an approximate frequency of 20%.
We propose a novel approach for clustering the vertices of a graph. The method, Vertex-Frequency Clustering (VFC), considers the local harmonic content of one or many graph signals, forming partitions based on spectra...
We propose a novel approach for clustering the vertices of a graph. The method, Vertex-Frequency Clustering (VFC), considers the local harmonic content of one or many graph signals, forming partitions based on spectral features in the input signal. The method can be related to spectral clustering, and the length scale over which frequencies are considered is tunable. This allows one to cluster data based on intrinsic graph geometry in the context of signal dynamics. VFC is useful for unravelling active regions in a signal, collecting sets of similar observations, or detecting anomalies. We demonstrate the utility of VFC in synthetic and biological data, and show how VFC can be used to identify observations with similar feature sets and signal profiles.
Ensembles have been increasingly used to represent the heterogeneity of protein native states and there is a number of exciting recent work that determines such ensembles using experimental *** what extent these ensem...
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Ensembles have been increasingly used to represent the heterogeneity of protein native states and there is a number of exciting recent work that determines such ensembles using experimental *** what extent these ensembles represent the native states is debatable since the ensemble,which may contain over a hundred conformations,may be underconstrained by the experimental *** this work,we introduce a new feature,the
Admixture mapping is a disease-mapping strategy to identify disease susceptibility variants in an admixed population that is a result of mating between 2 historically separated populations differing in allele frequenc...
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Admixture mapping is a disease-mapping strategy to identify disease susceptibility variants in an admixed population that is a result of mating between 2 historically separated populations differing in allele frequencies and disease prevalence. With the increasing availability of high-density genotyping data generated in genome-wide association studies, it is of interest to investigate how to apply admixture mapping in the context of the genome-wide association studies and how to adjust for admixture in association tests. In this study, we first evaluated 3 different local ancestry inference methods, LAMP, LAMP-LD, and MULTIMIX. Then we applied admixture mapping analysis based on estimated local ancestry. Finally, we performed association tests with adjustment for local ancestry.
Introduction: Middle ear volume(MEV) is a clinically relevant parameter across middle ear diseases. MEV values between these techniques have never before been tested for agreement in ears with perforated tympanic memb...
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Introduction: Middle ear volume(MEV) is a clinically relevant parameter across middle ear diseases. MEV values between these techniques have never before been tested for agreement in ears with perforated tympanic membranes(TMs).Methods: Middle ears were identified from 36 patients ranging 18-89 years of age with TM perforations who underwent tympanometry and temporal bone computed tomography(CT) between 2005 and 2015. MEVs calculated by both tympanometry and three-dimensional volume reconstruction(3DVR) were analyzed for agreement using Bland Altman plots. The differences between tympanometric and 3DVR MEV values for each given middle ear were characterized across MEV quartiles(1= smallest; 4= largest) and across increasing states of middle ear disease using Kruskale Wallis and Wilcoxon testing with Bonferroni ***: Bland Altman plots demonstrated significant disagreement between MEV measurement techniques. Differences between tympanometric(T) and 3DVR MEV values were significantly greater with increasing average(i.e.(Tt3DVR)/2)) MEV per linear regression(p < 0.0001). Significance was demonstrated between fourth and first average MEV quartiles(p= 0.0024), fourth and second quartiles(p= 0.0024), third and first quartiles(p= 0.0048), and third and second quartiles(p= 0.048). Absolute MEV difference was not significantly different across varying states of middle ear disease(p= 0.44).Conclusion: Statistically and clinically significant disagreement was demonstrated between tympanometric and 3DVR MEV values. Studies that vary in MEV estimation techniques may be expected to demonstrate significantly different results. These preliminary results suggest that clinicians should endeavor to seek further confirmation when interpreting high tympanometric MEV values.
Negative thermal expansion(NTE) behavior has roused wide interest for the control of thermomechanical properties of functional *** NTE behaviors have been found in kinds of compounds,it remains challenging for polymer...
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Negative thermal expansion(NTE) behavior has roused wide interest for the control of thermomechanical properties of functional *** NTE behaviors have been found in kinds of compounds,it remains challenging for polymers to achieve intrinsic NTE *** this work,we systematically studied the conformational change of dibenzocyclooctadiene(DBCOD) derivatives between chair(C) and twist-boat(TB) forms based on density-functional theo ry(DFT) calculations,and found clear evidence of the relationship between the structure of DBCOD units and the thermal contraction behavior of the related *** order to obtain the polymer with NTE property,two conditions should be met for the thermal contracting DBCOD related units as follows:(i) the TB conformation can turn into C conformation as the temperature increases,and(ii) the volume of C conformation is smaller than that of TB *** rule should offer a guidance to exploration of the new intrinsic NTE polymers in the future.
Background: CoreGenes3.5 is a webserver that determines sets of core genes from viral and small bacterial genomes as an automated batch process. Previous versions of CoreGenes have been used to classify bacteriophage ...
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